Effectiveness of a new vaccine for outbreak response and the increasingly complicated polio endgame
Authors: Kimberly M Thompson
Journal: The Lancet Global Health (2022)

Achieving the eradication of poliomyelitis remains an elusive goal. More than 6 years after the globally-coordinated cessation of all use of type 2 oral poliovirus vaccines (OPV2) in routine immunisation, outbreaks caused by type 2 circulating vaccine-derived polioviruses (cVDPV2s) continue to paralyse children and young adults around the world.1WHO Global Polio Eradication InitiativeGlobal circulating vaccine-derived poliovirus (cVDPV).https://polioeradication.org/wp-content/uploads/2022/10/weekly-polio-analyses-cVDPV-20221004.pdfDate: 2022Date accessed: October 4, 2022Google Scholar Since mid-2016, cVDPV2s have led to over 2650 reported cases of poliomyelitis (as of Oct 4, 2022),1WHO Global Polio Eradication InitiativeGlobal circulating vaccine-derived poliovirus (cVDPV).https://polioeradication.org/wp-content/uploads/2022/10/weekly-polio-analyses-cVDPV-20221004.pdfDate: 2022Date accessed: October 4, 2022Google Scholar with the majority (67%) in Africa.2Thompson KM Polio eradication: what kind of world do we want?.Lancet Infect Dis. 2022; 22: 161-163Summary Full Text Full Text PDF PubMed Scopus (9) Google Scholar A recent paralytic case (with onset of paralysis on June 20, 2022) in New York made the USA the 36th addition to the list of countries with reported cVDPV2 cases since 2016.1WHO Global Polio Eradication InitiativeGlobal circulating vaccine-derived poliovirus (cVDPV).https://polioeradication.org/wp-content/uploads/2022/10/weekly-polio-analyses-cVDPV-20221004.pdfDate: 2022Date accessed: October 4, 2022Google Scholar, 3Link-Gelles R Lutterloh E Schnabel Ruppert P et al.Public health response to a case of paralytic poliomyelitis in an unvaccinated person and detection of poliovirus in wastewater—New York, June-August 2022.MMWR Morb Mortal Wkly Rep. 2022; 71: 1065-1068Crossref PubMed Scopus (0) Google Scholar Transmission of type 1 wild polioviruses (WPV1s) and circulating vaccine-derived polioviruses (cVDPV1s) also continues, with 29 WPV1 cases reported in 2022 (as of October 4).4WHOWild poliovirus list: list of wild poliovirus by country and year.https://polioeradication.org/wp-content/uploads/2022/10/weekly-polio-analyses-WPV-20221004.pdfDate: 2022Date accessed: October 4, 2022Google Scholar Additionally, reported cases in 2022 caused by WPV1, cVDPV1, and cVDPV2 in Mozambique, and cVDPV1 and cVDPV2 in the Democratic Republic of the Congo, pose substantial challenges of responding to outbreaks of cocirculating different poliovirus types.1WHO Global Polio Eradication InitiativeGlobal circulating vaccine-derived poliovirus (cVDPV).https://polioeradication.org/wp-content/uploads/2022/10/weekly-polio-analyses-cVDPV-20221004.pdfDate: 2022Date accessed: October 4, 2022Google Scholar, 4WHOWild poliovirus list: list of wild poliovirus by country and year.https://polioeradication.org/wp-content/uploads/2022/10/weekly-polio-analyses-WPV-20221004.pdfDate: 2022Date accessed: October 4, 2022Google Scholar In the first few years after OPV2 cessation, doses of Sabin type 2 monovalent OPV (mOPV2) from a stockpile controlled by the WHO Director General created before 2016 served as the only vaccine available for cVDPV2 outbreak response.5WHO Global Polio Eradication InitiativeStrategy for the response to type 2 circulating vaccine-derived poliovirus 2020–2021: addendum to the polio eradication and endgame strategic plan (2019-2023).http://polioeradication.org/wp-content/uploads/2020/04/Strategy-for-the-response-to-type-2-circulating-Vaccine-Derived-Poliovirus-20200406.pdfDate: 2020Date accessed: March 10, 2020Google Scholar However, because of the cVDPV2 outbreaks in 2019, including a cVDPV2 outbreak in Pakistan (a WPV1-endemic country),6Macklin GR O'Reilly KM Grassly NC et al.Evolving epidemiology of poliovirus serotype 2 following withdrawal of the serotype 2 oral poliovirus vaccine.Science. 2020; 368: 401-405Crossref PubMed Scopus (71) Google Scholar concerns about limited OPV2 supplies in this stockpile motivated the new production of mOPV2 and trivalent OPV (tOPV; containing all three OPV types) in 2020.5WHO Global Polio Eradication InitiativeStrategy for the response to type 2 circulating vaccine-derived poliovirus 2020–2021: addendum to the polio eradication and endgame strategic plan (2019-2023).http://polioeradication.org/wp-content/uploads/2020/04/Strategy-for-the-response-to-type-2-circulating-Vaccine-Derived-Poliovirus-20200406.pdfDate: 2020Date accessed: March 10, 2020Google Scholar At the same time, efforts to develop and mass produce novel OPV2 (nOPV2) accelerated.7Macklin G Peak C Eisenhawer M et al.Enabling accelerated vaccine roll-out for public health emergencies of international concern (PHEICs): novel oral polio vaccine type 2 (nOPV2) experience.Vaccine. 2022; (published online March 17.)https://doi.org/10.1016/j.vaccine.2022.02.050Crossref Scopus (17) Google Scholar Notably, the Global Polio Eradication Initiative made an addendum to its Polio Endgame Strategy 2019–2023, which anticipated a prominent role for nOPV2 in outbreak response, with nOPV2 expected to replace mOPV2 for outbreak response by mid-2021.5WHO Global Polio Eradication InitiativeStrategy for the response to type 2 circulating vaccine-derived poliovirus 2020–2021: addendum to the polio eradication and endgame strategic plan (2019-2023).http://polioeradication.org/wp-content/uploads/2020/04/Strategy-for-the-response-to-type-2-circulating-Vaccine-Derived-Poliovirus-20200406.pdfDate: 2020Date accessed: March 10, 2020Google Scholar At its October 2020 meeting, the WHO Strategic Advisory Group of Experts on Immunization identified nOPV2 as a vaccine of choice for responding to cVDPV2 outbreaks.7Macklin G Peak C Eisenhawer M et al.Enabling accelerated vaccine roll-out for public health emergencies of international concern (PHEICs): novel oral polio vaccine type 2 (nOPV2) experience.Vaccine. 2022; (published online March 17.)https://doi.org/10.1016/j.vaccine.2022.02.050Crossref Scopus (17) Google Scholar In November 2020, WHO granted an Emergency Use Listing (EUL) for nOPV2 in outbreak response campaigns.7Macklin G Peak C Eisenhawer M et al.Enabling accelerated vaccine roll-out for public health emergencies of international concern (PHEICs): novel oral polio vaccine type 2 (nOPV2) experience.Vaccine. 2022; (published online March 17.)https://doi.org/10.1016/j.vaccine.2022.02.050Crossref Scopus (17) Google Scholar Nearly 2 years after the EUL, Azamdzhon Mirzoev and colleagues report serological study results of nOPV2 outbreak response campaigns with high coverage in Tajikistan in this issue of Lancet Global Health.8Mirzoev A Macklin GR Zhang Y et al.Assessment of serological responses following vaccination campaigns with type 2 novel oral polio vaccine: a population-based study in Tajikistan in 2021.Lancet Glob Health. 2022; 10: e1807-e1814Summary Full Text Full Text PDF PubMed Scopus (7) Google Scholar The study enrolled 228 children born since Jan 1, 2016, from seven districts in Tajikistan that had cVDPV2 transmission.8Mirzoev A Macklin GR Zhang Y et al.Assessment of serological responses following vaccination campaigns with type 2 novel oral polio vaccine: a population-based study in Tajikistan in 2021.Lancet Glob Health. 2022; 10: e1807-e1814Summary Full Text Full Text PDF PubMed Scopus (7) Google Scholar Seroprevalence of type 2 polio antibodies for vaccine recipients increased from 26% (95% CI 20–33) before the first dose of nOPV2, to 77% (70–82) after one dose, and to 83% (78–88) after the second dose.8Mirzoev A Macklin GR Zhang Y et al.Assessment of serological responses following vaccination campaigns with type 2 novel oral polio vaccine: a population-based study in Tajikistan in 2021.Lancet Glob Health. 2022; 10: e1807-e1814Summary Full Text Full Text PDF PubMed Scopus (7) Google Scholar The children born before the switch from tOPV to bivalent OPV showed substantially higher type 2 polio immunity at the beginning of the study, with 63% seroprevalence for children aged 62–66 months at enrolment compared with 33% for children aged 0–6 months, 29% for children aged 7–12 months, 15% for children aged 13–36 months, and 26% for children aged 37–61 months at enrolment.8Mirzoev A Macklin GR Zhang Y et al.Assessment of serological responses following vaccination campaigns with type 2 novel oral polio vaccine: a population-based study in Tajikistan in 2021.Lancet Glob Health. 2022; 10: e1807-e1814Summary Full Text Full Text PDF PubMed Scopus (7) Google Scholar The baseline seroprevalence revealed a lower than expected effect of inactivated poliovirus vaccine (IPV), delivered in routine immunisation, compared with reported coverage.8Mirzoev A Macklin GR Zhang Y et al.Assessment of serological responses following vaccination campaigns with type 2 novel oral polio vaccine: a population-based study in Tajikistan in 2021.Lancet Glob Health. 2022; 10: e1807-e1814Summary Full Text Full Text PDF PubMed Scopus (7) Google Scholar Additionally, this baseline seroprevalence probably also included some unknown numbers of children who received IPV as part of the initial outbreak response or who serologically converted in response to infection with cVDPV2.8Mirzoev A Macklin GR Zhang Y et al.Assessment of serological responses following vaccination campaigns with type 2 novel oral polio vaccine: a population-based study in Tajikistan in 2021.Lancet Glob Health. 2022; 10: e1807-e1814Summary Full Text Full Text PDF PubMed Scopus (7) Google Scholar The results of this study demonstrated that high coverage campaigns using nOPV2 offer an effective tool for responding to cVDPV2 outbreaks.8Mirzoev A Macklin GR Zhang Y et al.Assessment of serological responses following vaccination campaigns with type 2 novel oral polio vaccine: a population-based study in Tajikistan in 2021.Lancet Glob Health. 2022; 10: e1807-e1814Summary Full Text Full Text PDF PubMed Scopus (7) Google Scholar Although the study answers some questions for countries contemplating or currently using nOPV2, further studies will need to address remaining questions about nOPV2 performance. Notably, the detection of cVDPV2 cases and transmission after the second nOPV2 campaign in Tajikistan that motivated a third nOPV2 campaign8Mirzoev A Macklin GR Zhang Y et al.Assessment of serological responses following vaccination campaigns with type 2 novel oral polio vaccine: a population-based study in Tajikistan in 2021.Lancet Glob Health. 2022; 10: e1807-e1814Summary Full Text Full Text PDF PubMed Scopus (7) Google Scholar might hint at lower population immunity effectiveness for nOPV2 than mOPV2. The choice of low-titre candidate 1 nOPV2 for the EUL decreases shedding by vaccine recipients,9Gast C Bandyopadhyay AS Sáez-Llorens X et al.Fecal shedding of 2 novel live attenuated oral poliovirus type 2 vaccine candidates by healthy infants administered bivalent oral poliovirus vaccine/inactivated poliovirus vaccine: 2 randomized clinical trials.J Infect Dis. 2022; 226: 852-861Crossref PubMed Scopus (7) Google Scholar which might reduce its ability to induce immunity in populations through secondary spread, and its ability to compete with cocirculating viruses. Additionally, genetically engineering nOPV2 to remain more stable, and thus less likely to evolve and gain fitness as it transmits, might independently also lead to lower effectiveness with respect to population immunity in outbreak response campaigns.10Kalkowska DA Pallansch MA Wilkinson A et al.Updated characterization of poliovirus outbreak response strategies for 2019-2029: impacts of the use of novel OPV2 strains.Risk Anal. 2021; 41: 329-348Crossref PubMed Scopus (26) Google Scholar Either or both effects might necessitate achieving higher nOPV2 coverage to stop transmission than required using mOPV2. Without a study providing direct comparison between nOPV2 and mOPV2, decision makers might face challenges with respect to adjusting their outbreak response plans and managing expectations about nOPV2 performance. However, as Mirzoev and colleagues demonstrate, nOPV2 very effectively induces immunity in individual vaccine recipients and it is already proving its ability to stop some cVDPV2s.8Mirzoev A Macklin GR Zhang Y et al.Assessment of serological responses following vaccination campaigns with type 2 novel oral polio vaccine: a population-based study in Tajikistan in 2021.Lancet Glob Health. 2022; 10: e1807-e1814Summary Full Text Full Text PDF PubMed Scopus (7) Google Scholar I declare no competing interests. Assessment of serological responses following vaccination campaigns with type 2 novel oral polio vaccine: a population-based study in Tajikistan in 2021Our study demonstrated strong immune responses following nOPV2 outbreak response campaigns in Tajikistan. Our results support previous clinical trial data on the generation of poliovirus type 2 immunity by nOPV2 and provide evidence that nOPV2 can be appropriate for the cVDPV2 outbreak response. The licensure and WHO prequalification of nOPV2 should be accelerated to facilitate wider use of the vaccine. Full-Text PDF Open Access